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Medical management of abortion
Medical management of abortion, 2018
ISBN 978-92-4-155040-6
© World Health Organization 2018
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Printed in Switzerland.
Medical management of abortion
ii
Contents
iii
Web annexes: Medical management of abortion: evidence base (available at http://www.who.int/reproductivehealth/publications/medical-management-abortion/en/).
Acknowledgements ..................................................................... iv
Acronyms and abbreviations ....................................................... iv
Glossary ......................................................................................... v
Executive summary ...................................................................... vi
Rationale for this guideline viii
Guideline development process viii
Overview of recommendations x
Notable differences between this guideline and previous guidance xii
Estimation of duration of pregnancy (gestation) xiii
1. Introduction ........................................................................... xiv
1.1 Background 1
1.2 Goal and objectives 4
1.3 Target audience and relevance 5
2. Guideline development process............................................... 6
2.1 Contributors and their roles 7
2.2 Declarations of interests 8
2.3 Scoping and formulation of the guideline questions 9
2.4 Evidence retrieval and synthesis 10
2.5 Use of the frameworks for decision-making 11
2.6 Document preparation, revision and peer review 11
3. Recommendations, rationale and evidence summary .......... 12
3.1 Guiding principles 14
3.2 Incomplete abortion 16
3.3 Intrauterine fetal demise 22
3.4 Induced abortion 26
3.5 Post-abortion contraception 31
4. General implementation considerations .............................. 38
5. Dissemination and adaptation .............................................. 44
6. Guideline impact evaluation and future updates ................. 44
References ................................................................................... 46
Annex 1: WHO staff and external experts involved
in the guideline development process ....................................... 50
iv
AcknowledgementsThe guideline was developed by the Department of Reproductive Health and Research, World Health Organization.
WHO is grateful for the contributions of staff and consultants to the Department, members of the
Guideline Development Group and the external peer reviewers who participated in initial online consultations,
subsequent technical consultations and the review of this guideline.
A complete list of contributors and their specific roles can be found in Annex 1.
The development of these guidelines was supported by the UNDP-UNFPA-UNICEF-WHO-World Bank Special
Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored
programme executed by the World Health Organization (WHO).
Editing and proofreading: Green Ink, United Kingdom (greenink.co.uk).
Design and layout: Little Unicorns (https://littleunicorns.com).
Acronyms and abbreviations
B buccal (in the cheek) (route of administration of medication)
CDC Centers for Disease Control and Prevention
CRE Office of Compliance, Risk Management and Ethics
COI conflict of interest
DMPA depot medroxyprogesterone acetate
DOI declaration of interest
ERG External Review Group
EST Evidence Synthesis Team
EtD Evidence to Decision
GDG Guideline Development Group
GRADE Grading of Recommendations Assessment, Development and Evaluation
hCG human chorionic gonadotrophin
IM intramuscular
IUD intrauterine device
IUFD intrauterine fetal demise
LMP last menstrual period
NGO nongovernmental organization
PAHO Pan American Health Organization
PICO population, intervention, comparator, outcome
PO oral (route of administration of medication)
PV vaginal (route of administration of medication)
RCT randomized controlled trial
SL sublingual (under the tongue) (route of administration of medication)
WHO World Health Organization
v
GlossaryDuration of pregnancy (gestation): Size of the uterus, estimated in weeks, based on clinical examination,
that corresponds to a pregnant uterus of the same gestational age dated by last menstrual period (LMP).
Medical methods of abortion (medical abortion): Use of pharmacological drugs to terminate
pregnancy. Sometimes the terms “non-surgical abortion” or “medication abortion” are also used.
Routes of misoprostol administration:
oral pills are swallowed;
buccal pills are placed between the cheek and gums and swallowed after 30 minutes;
sublingual pills are placed under the tongue and swallowed after 30 minutes;
vaginal pills are placed in the vaginal fornices (deepest portions of the vagina) and the individual
is instructed to lie down for 30 minutes.
Surgical methods of abortion (surgical abortion): use of transcervical procedures for terminating
pregnancy, including vacuum aspiration and dilatation and evacuation (D&E). See Chapter 2, section 2.2.4 in
the WHO Safe abortion guideline (2012)1 for a more detailed description of methods of surgical abortion.
Human rights terminology
International human rights treaty/covenant/convention: adopted by the international community of
States, normally at the United Nations General Assembly. Each treaty sets out a range of human rights, and
corresponding obligations which are legally binding on States that have ratified the treaty. Annex 7 in the
2012 Safe abortion guideline includes a list of these treaties.
Regional human rights treaties: States adopted human rights treaties in Africa, the Americas, Europe
and the Middle East. Regional human rights bodies, such as the African Union, the Organization of
American States, the Council of Europe, the European Union, and the League of Arab States monitor
States’ compliance with the treaties. To date, there are no regional human rights treaties in South-East
Asia or the Western Pacific. Annex 7 in the 2012 Safe abortion guideline includes a list of regional
human rights treaties.
Human rights standards: the meaning and scope of human rights as interpreted and applied by the
human rights bodies tasked with this work, e.g. international, regional and national courts, and human
rights committees.
1 Safe abortion: technical and policy guidance for health systems, second edition. Geneva: World Health Organization; 2012 (http://apps.who.int/iris/bitstream/handle/10665/70914/9789241548434_eng.pdf).
vi
Executive summary
vii
Medical abortion care encompasses the management of various
clinical conditions including spontaneous and induced abortion
(both viable and non-viable pregnancies), incomplete abortion and
intrauterine fetal demise, as well as post-abortion contraception.
Medical management of abortion generally involves either a
combination regimen of mifepristone and misoprostol or a
misoprostol-only regimen. Medical abortion care plays a crucial role
in providing access to safe, effective and acceptable abortion care.
In both high- and low-resource settings, the use of medical methods
of abortion have contributed to task shifting and sharing and more
efficient use of resources. Moreover, many interventions in medical
abortion care, particularly those in early pregnancy, can now be
provided at the primary-care level and on an outpatient basis, which
further increases access to care. Medical abortion care reduces the
need for skilled surgical abortion providers and offers a non-invasive
and highly acceptable option to pregnant individuals.
viii
Exec
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yRationale for
this guidelineRecommendations for the use of mifepristone and misoprostol
for inducing abortion and for managing incomplete abortion are
contained within the 2012 WHO guideline Safe abortion: technical and
policy guidance for health systems. Evidence related to home use of
medication and self-assessment is included in the 2015 WHO guideline
Health worker roles in providing safe abortion and post-abortion
contraception. However, a number of new studies have been published
in more recent years providing evidence related to the timing, dosage,
dosing intervals and routes of administration of medications to manage
abortion, and also the timing of contraception initiation following a
medical abortion. Hence it was critical for WHO to review the evidence
and update its own recommendations.
Guideline development process
The guideline was developed according to the principles set out in the
WHO handbook for guideline development and under the oversight of
the WHO Guidelines Review Committee. The core team at WHO (the
Steering Group) was complemented by an Evidence Synthesis Team
(EST) of experts (including two guideline methodologists) and by a
multidisciplinary group of external technical experts who constituted
the Guideline Development Group (GDG).
The WHO 2012 Safe abortion guidance will be updated during 2019–2020.
The contents of this 2018 guideline represent prioritized thematic areas
that need to be updated more urgently, based on input from a pre-scoping
online survey, conducted in mid-2016 among a group of experts in
the field, and from a technical consultation and scoping meeting held
in February 2017. Based on input received, the WHO Steering Group
drafted an initial list of thematic issues and associated questions in PICO
(population, intervention, comparator, outcome) format. These thematic
issues included surgical management of abortion; however, the focus of
this clinical guideline is medical management of abortion. A systematic
literature search was conducted followed by review of the evidence;
eight separate systematic reviews were undertaken. Data that informed
the recommendations in this guideline came from a total of 140 studies
carried out in a wide variety of settings ranging from high- to low-income
economies. Figure 1 shows the geographical spread and number of studies
per indication for medical management of abortion that served as the
evidence base. The certainty of the evidence on safety, effectiveness and
user satisfaction was assessed using the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) approach.2
2 Further information is available at: http://www.gradeworkinggroup.org/
ix
Recommendations were finalized in consultation with the GDG
and using Evidence to Decision (EtD) frameworks that considered
benefits, harms, values, equity, feasibility and acceptability, as well
as implications for resource use, where available. Where there was
limited evidence, supplemental programmatic information provided by
experts from the field was considered. The guideline was prepared by
the WHO Steering Group with input from the GDG. In addition to the
GDG, several external peer reviewers who were unconnected to the
guideline development process also reviewed and critically appraised
the draft guideline prior to its finalization. Declarations of interest
(DOIs) were managed according to standard procedures.
RESOLUTION OF INCOMPLETE ABORTION 24 studies
Australia, Burkina Faso, China, Denmark, Egypt, Finland, Ghana, India, Madagascar, Mauritania, Mozambique, Niger, Nigeria, Republic of Maldova, Senegal, South Africa, Sweden, Thailand, Turkey, Uganda, United Kingdom, United Republic of Tanzania, United States of America (USA), Viet Nam
INDUCED ABORTION FOR FETAL DEMISE 16 studies
Australia, India, Iran, Netherlands, Pakistan, Sudan, Thailand, Turkey, USA, Viet Nam
INDUCED ABORTION < 12 WEEKS 49 studies
Armenia, Canada, China, Cuba, Georgia, Hong Kong SAR, Hungary, India, Iran, Kazakhstan, Mongolia, Mozambique, Nepal, Republic of Moldova, Romania, Scotland, Serbia, Slovenia, South Africa, Sweden, Thailand, Tunisia, Ukraine, United Kingdom, USA, Viet Nam
INDUCED ABORTION ≥ 12 WEEKS 44 studies
Australia, Armenia, Canada, China, Cuba, Finland, Georgia, Hungary, Hong Kong SAR, India, Nepal, New Zealand, Singapore, Slovenia, South Africa, Sweden, Thailand, Tunisia, Turkey, United Kingdom, USA, Uzbekistan, Viet Nam
TIMING OF POST-ABORTION CONTRACEPTION 7 studies
Finland, Mexico, Portugal, Sweden, United Kingdom, USA
FIGURE 1 Evidence base informing the recommendations
x
Exec
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yOverview of
recommendationsThis guideline focuses exclusively on medical management of abortion.
It provides new recommendations related to the following indications:
medical management of incomplete abortion at ≥ 13 weeks of gestation3
(Recommendation 1b), medical management of intrauterine fetal demise
at ≥ 14 to ≤ 28 weeks of gestation (Recommendation 2), timing of
post-abortion hormonal contraception initiation (Recommendation 4a)
and timing of post-abortion IUD placement (Recommendation 4b).
In addition, this guideline includes updated recommendations related
to the following indications: medical management of incomplete
abortion at < 13 weeks of gestation (Recommendation 1a), and medical
management of induced abortion at < 12 weeks (Recommendation 3a)
and at ≥ 12 weeks (Recommendation 3b).
³ Duration of pregnancy (gestation): Size of the uterus, estimated in weeks, based on clinical examination, that corresponds to a pregnant uterus of the same gestational age dated by last menstrual period (LMP).
RECOMMENDATIONSCOMBINATION REGIMEN
(RECOMMENDEDª)
MISOPROSTOL-ONLY
(ALTERNATE)
MIFEPRISTONE MISOPROSTOL MISOPROSTOL
1A. INCOMPLETE ABORTION
< 13 WEEKSNone
Use misoprostol-only
regimen
600 μg POb or 400 μg SLb
1B. INCOMPLETE ABORTION
≥ 13 WEEKSNone
Use misoprostol-only
regimen
400 μg B, PV or SL
every 3 hoursb
2. INTRAUTERINE FETAL DEMISE
≥ 14–28 WEEKS200 mg PO once
400 μg PV or SL
every 4–6 hoursb
400 μg SL (preferred) or PV every 4–6 hoursb
3A. INDUCED ABORTION
< 12 WEEKS200 mg PO once
800 μg B, PV or SLb
800 μg B, PV or SLb
3B. INDUCED ABORTION ≥ 12 WEEKS
200 mg PO once
400 μg B, PV or SL
every 3 hoursb
400 μg B, PV or SL
every 3 hoursb
TIMING OF POST-ABORTION CONTRACEPTION
IMMEDIATE INITIATION
4A. HORMONAL CONTRACEPTION Immediately after the first pill of the medical abortion
4B. IUD With assessment of successful abortion
xi
B: buccal ; PO: oral ; PV: vaginal ; SL: subl ingual
a Combinat ion regimen is recommended because i t is more effect ive.
b Repeat doses of misoprostol can be considered when needed to achieve success of the abort ion process. In this guidel ine we do not provide a maximum number of doses of misoprostol . Health-care providers should use caut ion and c l in ical judgement to decide the maximum number of doses of misoprostol in pregnant indiv iduals with pr ior uter ine incis ion. Uter ine rupture is a rare compl icat ion; c l in ical judgement and health system preparedness for emergency management of uter ine rupture must be considered with advanced gestat ional age.
1–2 DAYS
TABLE 1 Summary chart of recommendations on medical management of abortion
xii
Exec
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yNotable differences
between this guideline and previous guidance
There are several notable differences between this guideline and
previous (2012) WHO guidance, including the time period between
mifepristone and misoprostol dosing, the use of a loading dose, and
the maximum number of doses of misoprostol.
4 Safe abortion: technical and policy guidance for health systems, second edition. Geneva: World Health Organization; 2012 (http://www.who.int/reproductivehealth/publications/unsafe_abortion/9789241548434/en/).
TOPIC THIS GUIDELINE (2018) SAFE ABORTION GUIDELINE (2012)4
TIME PERIOD BETWEEN MIFEPRISTONE AND MISOPROSTOL DOSING
Time period is in days rather than hours
Time was provided in hours (i.e. 36–48) for induced abortion regimens with pregnancies beyond nine weeks
LOADING DOSE The use of a loading dose of misoprostol is not necessary
Previous guidance recommended a loading dose that differed from subsequent doses of misoprostol for induced abortion regimens with pregnancies beyond nine weeks
MAXIMUM NUMBER OF DOSES OF MISOPROSTOL
In this guideline we do not provide a maximum number of doses of misoprostol
Previous guidance recommended a maximum number of five doses
TABLE 2Notable differences between information in this guideline and previous guidance
xiii
Estimation of duration of pregnancy (gestation)
In this guideline, duration of pregnancy (gestation) is the size of
the uterus, estimated in weeks, based on clinical examination, that
corresponds to a pregnant uterus of the same gestational age dated
by last menstrual period (LMP). Where it is difficult to determine
uterine size based on clinical examination, alternate methods of
pregnancy dating can be used (i.e. LMP or ultrasound).
LIMITATIONS TO DATING BY UTERINE SIZE ON PHYSICAL EXAMINATION
KEY CONSIDERATIONS
A UTERUS THAT IS SMALLER THAN EXPECTED MAY INDICATE:
A UTERUS THAT IS LARGER THAN EXPECTED MAY INDICATE:
• uterine malformations/fibroids
• multiple gestation
• marked uterine retroversion
• obesity
• molar pregnancy
• the woman is not pregnant
• inaccurate menstrual dating
• ectopic pregnancy or abnormal intrauterine pregnancy, e.g. spontaneous or missed abortion
• inaccurate menstrual dating
• multiple gestation
• uterine abnormalities, such as fibroids
• molar pregnancy
UTERINE SIZE ( IN WEEKS)
AFTER 4 WEEKS OF GESTATION
THE UTERUS INCREASES IN SIZE BY
APPROXIMATELY 1 CM PER WEEK
AFTER 15–16 WEEKS OF GESTATION
THE UTERUS REACHES THE MIDPOINT BETWEEN
THE SYMPHYSIS PUBIS AND THE UMBILICUS
AFTER 12 WEEKS OF GESTATION
THE UTERUS RISES OUT OF THE PELVIS
AT 20 WEEKS OF GESTATION
THE UTERUS REACHES THE UMBILICUS
AFTER 20 WEEKS OF GESTATION
FUNDAL HEIGHT IN CENTIMETRES
MEASURED FROM THE SYMPHYSIS
PUBIS APPROXIMATES THE WEEKS
OF GESTATION
Source: Clinical practice handbook for safe abortion. Geneva: World Health Organization; 2014, p. 17 (http://www.who.int/reproductivehealth/publications/unsafe_abortion/clinical-practice-safe-abortion/en/); adapted from Goodman S, Wolfe M; TEACH Trainers Collaborative Working Group. Early abortion training workbook, third edition. San Francisco (CA): UCSF Bixby Center for Reproductive Health Research and Policy; 2007 (http://www.teachtraining.org/trainingworkbook/earlyabortiontrainingworkbook.pdf).
FIGURE 2Pregnancy dating by physical examination (bimanual pelvic and abdominal examination)
2 4 8 12 16 20 30 40
xiv
1. Introduction
1
1.1 Background Mifepristone and misoprostol in combination or misoprostol alone
are the medications generally used to induce abortion and to
manage incomplete abortion or intrauterine fetal demise (IUFD).
These medications are increasingly available globally, and they are on
the World Health Organization (WHO) List of Essential Medicines (1).
Mifepristone is an anti-progestin which binds to progesterone
receptors, inhibiting the action of progesterone and hence
interfering with the continuation of pregnancy. Treatment regimens
entail an initial dose of mifepristone followed by administration
of a synthetic prostaglandin analogue, misoprostol, which induces
cervical softening and dilation and enhances uterine contractions,
which aids in expelling the products of conception (2,3).
Misoprostol is a prostaglandin E1 analogue that can be used either in
combination with mifepristone or on its own (4–6). Misoprostol has
a wide range of reproductive health applications, including induction
of labour, management of spontaneous and induced abortion, and
prevention and treatment of postpartum haemorrhage (7). Due to
the ease of handling and storing it, as well as its non-invasiveness
and proven cost-effectiveness, the use of misoprostol within abortion
care – either in combination with mifepristone or alone – offers several
advantages. It reduces the need for skilled surgical abortion providers,
equipment, sterilization and anaesthesia, while offering a non-invasive
and highly acceptable option to pregnant individuals (8). For these
reasons, and because it is stable at room temperature within its
packaging, misoprostol is particularly useful in low-resource settings (7).
Medical abortion plays a crucial role in providing access to safe,
effective and acceptable abortion care. Previous guidance published
by WHO, including Safe abortion: technical and policy guidance for
health systems (2012), provided recommendations for the use of
mifepristone and misoprostol in combination or misoprostol alone for
the management of medical abortion (6). The 2012 guidance stated
that many interventions in medical abortion care, particularly those
2
Intr
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uct
ion
in early pregnancy, can be provided at the primary care level and on
an outpatient basis, which further increases access to care (6). In
both high- and low-resource settings, the use of medical methods
of abortion have contributed to task shifting and sharing and more
efficient use of resources (9). Given the nature of the medical abortion
process, it is also possible for individuals to play a role in managing
some of the components by themselves, outside of a health-care facility.
Another existing WHO guideline, Health worker roles in providing safe
abortion and post-abortion contraception (2015), recommends that in
specific circumstances, individuals may self-manage their mifepristone
and/or misoprostol medication without direct supervision of a
health-care provider, as well as self-assess the success of the abortion
process using pregnancy tests and checklists (10) (see Box 1). It should
be noted that pregnancy tests used to self-assess the success of the
abortion process are low-sensitivity urine pregnancy tests, which are
different from those tests commonly used to diagnose pregnancy. Such
self-assessment and self-management approaches can be empowering
for individuals and help to triage care, leading to a more optimal use of
health-care resources.
All individuals who can become pregnant, including women, girls
and those with varying gender identities, and who seek medical
abortion care should be provided with all of the necessary information
to make an informed decision to ensure the promotion of their
health and human rights, including sex and gender equality and
non-discrimination. With this information, individuals can decide freely
and responsibly the number, spacing and timing of their children (11).
It is the right of every person, regardless of marital status, to enjoy the
benefits of scientific progress and its applications (11).
Depending upon the context, unmarried individuals, adolescents,
those living in extreme poverty, individuals from ethnic minorities,
refugees and other displaced persons, people with disabilities, and
those facing violence in the home may be vulnerable to inequitable
access to safe abortion services. Adolescents, in particular, are less
likely than adults to be able to obtain legal and safe abortions
to terminate their pregnancies. Some of the barriers adolescents
face include requirements for third party authorizations (including
parental consent) and financial constraints (inability to pay the
required fees) (6,12). Additional considerations related to the care
of adolescents can be found in section 4 (General implementation
considerations), and in the WHO adolescent job aid (13).
Where geographic inequities exist, people must travel greater
distances for care, thereby raising costs and delaying access (14).
Financing mechanisms should ensure equitable access to
good-quality services (15). Where individuals are charged fees
for abortion, such fees should be matched to their ability to pay,
All individuals who can become pregnant, including women, girls and those with varying gender identities, and who seek medical abortion care should be provided with all of the necessary information to make an informed decision to ensure the promotion of their health and human rights, including sex and gender equality and non-discrimination.
3
and procedures should be developed for exempting the poor and
adolescents from paying for services. As far as possible, abortion
services should be mandated for coverage under insurance plans.
Abortion should never be denied or delayed because of inability to
pay. Providers of abortion services should ensure that all individuals
are treated with respect and without discrimination.
Health-care providers, health managers, policy-makers and other
stakeholders need up-to-date, evidence-based recommendations to
inform clinical policies and practices, to enable improved health-care
outcomes and to provide information that is complete, accurate
and easy to understand. Expansion of medical abortion and new
studies related to the timing, interval and routes of administration of
medical abortion medications, necessitated a review of the evidence
and the development of new recommendations as well as updates to
the WHO recommendations issued in 2012 (6).
PREVIOUS WHO RECOMMENDATIONS RELATED TO MEDICAL ABORTION CARE WERE PRESENTED
IN TWO WHO GUIDELINES, WHICH REMAIN CURRENT AND APPLICABLE:
Safe abortion: technical and policy guidance for health systems
This guideline was first issued in 2003 and the second edition was released in 2012 (updated based on evidence available for review in 2010). It provides recommendations for clinical care while addressing policy, programmatic and health systems considerations in the provision of safe abortion (6). Specific thematic areas related to medical abortion regimens contained within the 2012 edition have been updated in this 2018 guideline on the medical management of abortion; however, guidance on aspects of care provision (such as the service location and determination of success of medical abortion regimens) still apply, as presented in the 2012 guideline. These considerations have been placed in this 2018 guideline either in the “Additional considerations” subsections for each recommendation or in the “General implementation considerations” section, which follows the “Recommendations” section.
Health worker roles in providing safe abortion and post-abortion contraception
This guideline was issued in 2015 (with evidence up until 2015). It contains recommendations on the roles of various health workers involved in abortion care, as well as on self-management of medical abortion (10). These 2015 recommendations remain applicable, since this 2018 guideline on the medical management of abortion focuses solely on the medication regimens.
BOX 1 Other relevant WHO guidance on safe abortion
4
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od
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ion
1.2 Goal and objectives
Goal: To provide evidence-based recommendations on the safety and
effectiveness of abortion medications for the clinical management of
abortion, as well as the satisfaction of users.
Objectives: To review the evidence and develop (or update)
recommendations related to the following focus areas:
1. Medical management of incomplete abortion at < 13 weeks and at
≥ 13 weeks of gestation (updating the recommendations in the 2012
WHO Safe abortion guideline (6) based on new evidence);
2. Medical management of intrauterine fetal demise (IUFD) at
≥ 14 to ≤ 28 weeks of gestation (new recommendation as no
previous recommendations existed);
3. Medical management of induced abortion at < 12 weeks and at
≥ 12 weeks of gestation (updating the recommendations in the 2012
WHO Safe abortion guideline (6) based on new evidence);
4. Timing of initiation of contraception after medical abortion
(new recommendation as no previous recommendations existed).
In this guideline, duration of pregnancy (gestation) is the size of
the uterus, estimated in weeks, based on clinical examination, that
corresponds to a pregnant uterus of the same gestational age dated
by last menstrual period (LMP). Where it is difficult to determine
uterine size based on clinical examination, alternate methods of
pregnancy dating can be used (i.e. LMP or ultrasound). See also
Figure 2 in the Executive summary.
5
1.3 Target audience and relevance
The guideline is expected to be useful for:
health-care providers;
national and subnational policy-makers;
implementers and managers of national and subnational
reproductive health programmes; and
nongovernmental and other organizations and professional
bodies involved in the planning and management of medical
abortion services.
While legal, policy and regulatory contexts vary, abortion is legal at
least to save the life of the pregnant individual in most countries
and more than two thirds of countries have one or more additional
grounds for legal abortion (16). The provision of post-abortion care
is always legal (10). These recommendations will be relevant across
a diverse range of settings as the need to make care more accessible
and rationalize the use of available health resources exists in both
high- and low-resource settings.
6
2. Guideline development process
7
This guideline was developed by the WHO Department of Reproductive
Health and Research in accordance with procedures outlined in the
WHO handbook for guideline development, second edition, 2014 (17)
and under the oversight of the WHO Guidelines Review Committee.
Individuals from other organizations who contributed to this guideline did
so in their capacity as individual experts. Donors to the Department who
fund work on abortion issues were not included among the members of
the Guideline Development Group (GDG) and were not present at any of
the GDG meetings. Commercial entities were not involved in developing
the guideline, nor was funding from such sources used.
2.1 Contributors and their roles
The guideline was produced by the WHO Department of Reproductive
Health and Research and the work of developing the guideline was
coordinated by the WHO Steering Group, comprising WHO staff and
consultants. The Secretariat was formed of members of the Steering
Group from the Department of Reproductive Health and Research. The
Secretariat developed the guideline questions, oversaw and participated
in the evidence retrieval and synthesis, developed the Evidence to
Decision (EtD) frameworks and drafted the recommendations, while
also managing the day-to-day activities of developing the guideline.
The Evidence Synthesis Team (EST) consisted of several researchers,
who conducted the systematic reviews, and guideline methodologists,
who were responsible for evidence retrieval, synthesis and appraisal,
including assisting the Steering Group to develop the EtD frameworks.
The guideline methodologists were experts from the Global Health
Unit, Norwegian Institute of Public Health, Oslo, Norway, and
8
Pro
cess
Cochrane, Portland, United States of America (USA). They worked
closely with the WHO Steering Group and researchers from the EST to
appraise the evidence from the systematic reviews using Grading of
Recommendations Assessment, Development and Evaluation (GRADE)
methodology.5
The Guideline Development Group (GDG) was composed of 11 members
(5 women, 6 men) from various regions who possessed expertise on a
diverse range of relevant issues. GDG members were selected on the basis
of their particular knowledge of clinical care for abortion, service delivery
and health systems and their work in regions of the world where the need
for medical guidance on abortion care is a high priority. The GDG members
provided input into the development of the scope of the guideline, the
formulation of the population-intervention-comparator-outcome (PICO)
questions, the review of the evidence and the development of the
recommendations. They also reviewed and approved the final guideline.
A technical consultation and scoping meeting for this guideline was
held in Geneva, Switzerland, in February 2017. Further consultation was
conducted via email, and four subsequent GDG webinar meetings were
held, in December 2017, March 2018, June 2018 and August 2018.
Eight individuals, external to the guideline development process and
chosen to reflect the views of end-users who will be impacted by these
recommendations, served as an External Review Group (ERG) for the
draft guidelines.
A complete list of all contributors, their affiliations and roles is
provided in Annex 1.
2.2 Declarations of interests
In accordance with the WHO handbook for guideline development (17),
all members of the GDG, EST and ERG were required to complete the
standard WHO Declaration of Interests (DOI) form. GDG members
completed the form prior to each meeting they attended and were also
instructed to let the Secretariat know of any changes to their declared
interests over time. In addition, experts were requested to submit an
electronic copy of their curriculum vitae and their biographies (which were
posted online for a minimum of two weeks) along with the completed
DOI form prior to each meeting. The WHO Steering Group evaluated the
responses and discussed them with the Director of the WHO Department
of Reproductive Health and Research. At the GDG meetings, the Chair
presented a summary of the DOIs and all participants had the opportunity
to confirm, append or amend any interests already declared.
5 Further information is available at: http://www.gradeworkinggroup.org/
9
One individual being considered for the GDG declared an interest
that was perceived to be a potential conflict of interest for the
purpose of this guideline. This was discussed with the WHO Office
of Compliance, Risk Management and Ethics (CRE). Based on the
advice of the CRE, this individual was allowed to participate in the
meetings as a technical resource person but did not participate in
the development of the recommendations. No additional conflicts
of financial interests or involvement with commercial entities were
declared. The DOI forms and curriculum vitae have been electronically
archived to ensure that confidentiality is maintained.
2.3 Scoping and formulation of the
guideline questionsThe issues to be addressed by this guideline were carefully scoped and
refined. The initial list of concepts to be considered was developed on the
basis of the results of a pre-scoping online survey conducted in mid-2016,
which over 60 experts from all regions of the world were invited
to participate in. This survey aimed to identify relevant research
gaps and possible interventions. A total of 40 responses were received.
Further discussions were held via telephone or videoconference with the
respondents. Based on input received, the WHO Steering Group drafted
an initial list of thematic issues and associated questions in PICO
format. The draft list of PICO questions was presented at the technical
consultation and scoping meeting in February 2017. Most of those who
contributed to the development of the guideline, as listed in Annex 1, also
attended this meeting.
Preliminary PICO questions were identified, discussed, reviewed,
modified and finalized during the scoping meeting. The final PICO
questions for this guideline represent prioritized thematic areas that
needed to be updated most urgently, based on input during the
technical consultation and scoping meeting. The finalized priority
PICO questions covered the following thematic areas:
medical management of incomplete abortion
at ≥ 13 weeks of gestation;
medical management of intrauterine fetal demise (IUFD)
at ≥ 14 to ≤ 28 weeks of gestation;
medical management of induced abortion
at 9–12 weeks of gestation;
medical management of induced abortion
at ≥ 12 weeks of gestation;
timing of initiation of contraception after a medical abortion.
Several other thematic areas were noted as important, two of which
were re-addressed in an effort to provide a more comprehensive set of
10
Pro
cess
recommendations:
medical management of incomplete abortion at
< 13 weeks of gestation; and
medical management of induced abortion at
< 9 weeks of gestation.
The primary outcomes of interest were:
benefits and harms
• effectiveness (specific to the task) and
• safety, i.e. serious adverse events and complications
(specific to the task).
The secondary outcomes of interest were:
side-effects (specific to the intervention) and
satisfaction of users (specific to the intervention).
2.4 Evidence retrieval and synthesis
Evidence of safety, effectiveness and satisfaction related to the interventions
of interest included relevant randomized controlled trials (RCTs) as well
as non-randomized controlled trials, controlled before-and-after studies,
interrupted time-series and cohort studies. The following databases were
searched from inception to June 2017, without language filters.
International databases: ClinicalTrials.gov, Cochrane database,
Cumulative Index to Nursing and Allied Health Literature
(CINAHL), Embase, Global Index Medicus (GIM), Population
Information Online (POPLINE), PubMed.
Regional databases: African Index Medicus (AIM), Chinese
Biomedical Literature Database, Index Medicus for the South-East
Asian Region (IMSEAR), Index Medicus for the Eastern
Mediterranean Region (IMEMR), Latin American and Caribbean
Health Sciences Literature (LILACS), Western Pacific Regional
Index Medicus (WPRIM).
In addition, a search of trial registry sites and organizational websites,
as well as information from experts in the field, were used to identify
any major ongoing or completed but unpublished trials that could be
relevant to the guideline and the recommendations.
2.4.1 Assessment of confidence in the evidenceThe certainty (i.e. the extent to which one can be confident that an
estimate of the effect or association is correct) of the evidence on
the benefits and harms outcomes was assessed using the GRADE
approach; two GRADE methodologists were responsible for different
thematic issues. Five criteria – study limitations, consistency of effect,
imprecision, indirectness and publication bias – were used to assess the
certainty for each outcome. The level of certainty in the evidence was
downgraded by one level for serious limitations and by two levels for
11
very serious limitations. Information about the certainty of evidence can
be found in the justification section for each recommendation.
2.4.2 Moving from evidence to recommendationsVarious factors that inform decisions on recommendations were
assessed using the Evidence to Decision (EtD) framework method
developed by the DECIDE collaboration (18). Developing an EtD
framework requires explicit and systematic consideration of evidence
on interventions in terms of specified domains: effects (benefits/
harms), values, equity, resources required, acceptability (as distinct
from the secondary outcome of satisfaction) and feasibility.
Additional evidence of potential harms or unintended consequences
is described in the “Additional considerations” subsection of each
evidence summary. Such considerations include programmatic data
that did not directly address the priority PICO question but provided
pertinent information in the absence of direct evidence, and additional
data extracted from other relevant sources including qualitative studies.
2.5 Use of the frameworks for
decision-makingDraft EtD frameworks were prepared by the WHO Steering Group and
the EST. These were reviewed by the GDG and recommendations were
subsequently drafted and then were finalized during the four GDG
webinar meetings. In addition to the EtD frameworks, the GDG also
had access to all the supporting materials.
Decision-making (formulation of recommendations) was based on the
EtD frameworks and discussion of the synthesized evidence. The final
adoption of each recommendation was consensus-driven, defined as
full agreement among all GDG members, where possible. The final
decision was based on majority opinion, provided the GDG members with
opposing views were willing to agree to this outcome; voting to reach a
final decision was unnecessary. An option for noting dissenting opinions
was available, but at no time was it necessary to exercise this option.
2.6 Document preparation, revision
and peer reviewResponsible officers at WHO wrote the draft guideline. The GDG
reviewed the draft and their feedback was incorporated. The guideline
was also reviewed by the members of the ERG who were unconnected
with the process of guideline development. They provided structured
feedback on accuracy, presentation, implementation considerations
and the overall usefulness of the guideline.
12
3. Recommendations, rationale and evidence summary
13
Recommendations in this guideline focus on four thematic areas and
are presented here accordingly in subsections, as follows.
Recommendations on medical regimens for the management of:
1. incomplete abortion
2. intrauterine fetal demise (IUFD)
3. induced abortion.
Recommendations on the timing of:
4. initiation of contraception after medical abortion.
Following each recommendation, the rationale and evidence summary
are provided, followed by additional considerations and research gaps.
The research gaps were identified using a survey that was circulated
among the members of the Guideline Development Group (GDG) to
indicate topics requiring further research.
Considerations relating to care provision, including location of services,
provider type, assessment of success of the medical abortion regimen,
and the role of ultrasound, are derived from the 2012 WHO publication,
Safe abortion: technical and policy guidance for health systems (6).
Information on these considerations has been included in this
guideline under the “Additional considerations” subsections for each
recommendation and in the “General implementation considerations”
section, which follows this section on recommendations.
Recommendations in this guideline are presented using one of the
following phrases:
We recommend the intervention (strong recommendation in
favour of the intervention)
We suggest the intervention (weak, conditional, discretionary or
qualified recommendation in favour of the intervention)
Justifications for each recommendation are provided. The certainty of
the underlying body of evidence (high, moderate, low or very low) is
also specified.
14
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s3.1 Guiding principles
Principles underlying the process of improving the access to and
quality of abortion care include the right of access to relevant
evidence-based health information, so that individuals who can
become pregnant can have control over and decide freely and
responsibly on matters related to their sexuality and reproduction
(including their sexual and reproductive health) free of coercion,
discrimination and violence (11). These principles also include the
provision of additional services, for the holistic care of the patient.
3.1.1 Provide information Information is a necessary component of any medical care and should
always be provided to individuals considering abortion. At a minimum,
this should include (6):
the available options for abortion methods and pain
management;
what will be done before, during and after the procedure,
including any tests that may be performed;
what they are likely to experience (e.g. pain and bleeding) and
how long the procedure and the recovery are likely to take
(vaginal bleeding for two weeks is normal after medical abortion
– such bleeding can last up to 45 days in rare cases);
how to recognize potential complications, and how and where
to seek help, if required (individuals should return to the hospital
or clinic if they experience increased intensity of cramping or
abdominal pain, heavy vaginal bleeding and/or fever);
when normal activities can be resumed, including sexual
intercourse (the return of fertility can occur within two weeks
following abortion);
where and how to access additional services and follow-up care
(see section 3.1.4 on the right).
3.1.2 Offer counselling Counselling is a focused, interactive process through which one
voluntarily receives support, additional information and guidance
from a trained person, in an environment that is conducive to
openly sharing thoughts, feelings and perceptions. When providing
counselling, it is essential to:
communicate information in simple language;
maintain privacy;
support the individual and ensure they receive adequate
responses to their questions and needs; and
avoid imposing personal values and beliefs (6).
15
3.1.3 Additional servicesAdditional services may need to be provided to individuals seeking
medical abortion (19).
Provide iron tablets for anaemia, if needed.
Provide any necessary pain medications.
Provide emotional support, if needed.
Refer the individual to other services as determined by
an assessment of their needs; these services may include:
counselling and testing for sexually transmitted infections (STIs,
including HIV), abuse support services, psychological or social
services, or other specialist health or medical services.
3.1.4 Follow-up careRoutine follow-up is not necessary following an uncomplicated surgical
or medical abortion using mifepristone and misoprostol. However, an
optional follow-up visit 7–14 days after their procedure may be offered
to provide further contraceptive counselling and services, further
emotional support, or to address any medical concerns.
A routine follow-up visit is recommended only in the case of medical
abortion using misoprostol alone, to assess success of the abortion.
At the follow-up appointment:
assess the individual’s recovery and inquire about any signs
or symptoms of ongoing pregnancy;
review any available medical records and referral documents;
ask about any symptoms experienced since the procedure;
perform a focused physical examination in response to any
complaints; and
assess the individual’s fertility goals and need for
contraceptive services.
• If no method was started prior to discharge from the
facility, provide information and offer counselling and the
appropriate contraceptive method, if desired by the client.
• If a contraceptive method was already started, assess the
method used and note any concerns – where there are no
concerns, resupply as needed; where there are concerns,
help with selection of another appropriate method (19).
16
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s3.2 Incomplete
abortion
3.2.1 Diagnosis of incomplete abortionIncomplete abortion is defined by clinical presence of open cervical os
and bleeding, whereby all products of conception have not been
expelled from the uterus. Common symptoms include vaginal bleeding
and abdominal pain. Incomplete abortion should also be suspected if,
upon visual examination, the expulsed tissue is not consistent with the
estimated duration of pregnancy.
3.2.2 Medical management of incomplete abortion: Recommendations 1a and 1bIncomplete abortion may be managed expectantly, or treated
surgically or medically. The mode of management to be used
should be selected based on the individual’s clinical condition and
preference for treatment.
6 In this guideline, duration of pregnancy (gestation) is the size of the uterus, estimated in weeks, based on clinical examination, that corresponds to a pregnant uterus of the same gestational age dated by last menstrual period (LMP).
RECOMMENDATIONS COMBINATION REGIMEN MISOPROSTOL-ONLY
MIFEPRISTONE MISOPROSTOL MISOPROSTOL
INCOMPLETE ABORTION
< 13 WEEKSNone
Use misoprostol-only
regimen
600 μg POa or 400 μg SLa
a Repeat doses of misoprostol can be considered when needed to achieve success of the abort ion process. In this guidel ine we do not provide a maximum number of doses of misoprostol . Health-care providers should use caut ion and c l in ical judgement to decide the maximum number of doses of misoprostol in pregnant indiv iduals with pr ior uter ine incis ion. Uter ine rupture is a rare compl icat ion; c l in ical judgement and health system preparedness for emergency management of uter ine rupture must be considered with advanced gestat ional age.
1–2 DAYS
RECOMMENDATION 1AMedical management of incomplete abortion at < 13 weeks of gestation6
PO: oral ; SL: subl ingual
For the treatment of incomplete abortion at < 13 weeks uterine size, we suggest the use of 600 μg misoprostol administered orally or 400 μg misoprostol administered sublingually.a
RECOMMENDATION TYPE: NEW OR UPDATED
Recommendation 1a is an updated recommendation from the WHO 2012 Safe abortion guidance (6). The option of 400–800 μg vaginal misoprostol has been removed from this updated recommendation.
17
3.2.3 Evidence summary and rationale for Recommendations 1a and 1bA Cochrane review served as the evidence base for the medical
management of incomplete abortion; the review assessed the
effectiveness, safety and acceptability of various management
options (20). There were 24 studies included in the review that
focused on incomplete abortion at < 13 weeks of gestation.
Of those 24 studies, 22 compared different doses and routes of
misoprostol in misoprostol-only regimens and options of expectant,
medical or surgical management.
Effects (benefits and harms) Two studies focused on misoprostol dosage regimens; these studies
found higher rates of successful abortion and fewer unplanned
surgical interventions with 600 μg repeat oral dosing. In the studies
that compared misoprostol routes, there was no clear evidence of one
route being superior to another. In the studies that compared medical
management with surgical or expectant management, the incidence
RECOMMENDATIONS COMBINATION REGIMEN MISOPROSTOL-ONLY
MIFEPRISTONE MISOPROSTOL MISOPROSTOL
INCOMPLETE ABORTION
≥ 13 WEEKSNone
Use misoprostol-only
regimen
400 μg B, PV or SL
every 3 hoursa
1–2 DAYS
RECOMMENDATION 1BMedical management of incomplete abortion at ≥ 13 weeks of gestation
B: buccal ; PV: vaginal ; SL: subl ingual
For the treatment of incomplete abortion at ≥ 13 weeks uterine size, we suggest the use of repeat doses of 400 μg misoprostol administered sublingually, vaginally or buccally every 3 hours.a
RECOMMENDATION TYPE: NEW OR UPDATED
Recommendation 1b is a new recommendation.
a Repeat doses of misoprostol can be considered when needed to achieve success of the abort ion process. In this guidel ine we do not provide a maximum number of doses of misoprostol . Health-care providers should use caut ion and c l in ical judgement to decide the maximum number of doses of misoprostol in pregnant indiv iduals with pr ior uter ine incis ion. Uter ine rupture is a rare compl icat ion; c l in ical judgement and health system preparedness for emergency management of uter ine rupture must be considered with advanced gestat ional age.
18
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sof successful abortion was found to be slightly lower with medical
and expectant management, but all methods achieved high success
rates. In all 22 studies that looked at the relevant regimens, there
were few data on serious adverse events.
There were no studies that focused exclusively on incomplete abortion
at ≥ 13 weeks. One study set in Finland evaluated the management
of incomplete abortion in pregnancies up to 24 weeks of gestation,
but it included only three women whose pregnancies fell within the
gestational age between 13 and 24 weeks by menstrual dating (21).
Of these three women, one received medical treatment and the other
two received surgical intervention.
Values There was no evidence identified in the Cochrane review that looked
directly at how women value medical abortion procedures. However,
generally, women describe avoidance of surgery as a positive feature
of medical management, while some women value the shorter
abortion process and minimal bleeding associated with surgical
management (22,23). Some women dislike the side-effects associated
with medical management, including bleeding, fevers and chills (22,23).
Equity We were unable to identify research on aspects of equity relating to the
relative effectiveness of the intervention in different subgroups; no
assumptions were made.
Resources We attempted to collect programmatic data from organizations
involved in service delivery in order to inform the decision on how
resources factor into the recommendation. However, we were only
able to collect limited information, and the available data varied
considerably in its reporting (e.g. definition of terms), thus these
data were not used in the decision-making. In cases where additional
hospital resources are required, such as blood transfusion, inpatient
management or analgesic measures, we assume that the costs
associated with this care will be higher.
Acceptability Women generally find medical management of incomplete abortion with
misoprostol alone acceptable and would recommend the procedure to
a friend (24–27).
Feasibility We were unable to identify research on the feasibility of implementing
the use of misoprostol alone or in combination with mifepristone for
the management of incomplete abortion. However, the Cochrane
review included 22 studies conducted across 24 countries, providing
information related to the varying country contexts in which such
services may be provided. Of these 24 countries, seven were
in low-income economies, seven were in lower-middle-income
economies, four were in upper-middle-income economies and
six were in high-income economies (20).
19
Rationale for Recommendation 1a (on incomplete abortion
at < 13 weeks): Women treated with 600 μg oral misoprostol
had higher rates of successful abortion and lower occurrence of
additional surgical interventions; this is based on low-certainty
evidence. Low-certainty evidence also suggests that the use of
400 μg sublingual misoprostol leads to high rates of successful
abortion. Acceptability of these regimens also appears high.
Rationale for Recommendation 1b (on incomplete abortion
at ≥ 13 weeks): Due to the lack of direct evidence on medical
management of incomplete abortion at ≥ 13 weeks of gestation, this
recommendation is based on information extrapolated from data related
to the medical management of abortion at > 12 weeks using misoprostol
alone. Individuals presenting with incomplete abortion at ≥ 13 weeks
may present with varying amounts of residual tissue or products of
conception. Thus, the GDG members took the view that since the
regimen utilized for medical abortion at > 12 weeks is safe, effective and
acceptable, then this regimen can also be applied to those being treated
for incomplete abortion where expulsion of uterine contents has begun,
as evidenced by bleeding, cramping or contractions.
3.2.4 Additional considerationsUltrasound scanning is not routinely required for the provision of
abortion (4,28,29). Ultrasound is useful to detect ongoing pregnancy;
measuring endometrial thickness, however, is not generally useful
for diagnosing incomplete abortion and may lead to inappropriate
surgical interventions (30).
The following health worker cadres can provide medical management
of uncomplicated incomplete abortion, given task-specific training and
functioning systems for monitoring and supportive supervision: auxiliary
nurses, auxiliary nurse midwives, nurses, midwives, associate/advanced
associate clinicians, and non-specialist and specialist doctors (10).
3.2.5 Research gapsGeneral:
Identification of the most effective medical abortion regimen
for incomplete abortion at ≥ 13 weeks of gestation (including
the use of mifepristone in combination with misoprostol versus
misoprostol alone) is still needed. Recommendations have been
made for this regimen using indirect evidence. Results from the
survey on research gaps (completed by GDG members) noted the
lack of evidence for effective regimens in this clinical scenario
and, therefore, further research on this topic should be pursued.
20
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s3.3 Intrauterine
fetal demise
3.3.1 Diagnosis of intrauterine fetal demise (IUFD)Fetal demise refers to situations in which the fetus is no longer
alive, but the uterus has not yet started to expel its contents and the
cervical os remains closed (31). The diagnosis is made by ultrasound
scan following the clinical findings, which can include vaginal
bleeding, absent fetal heart sounds on electronic auscultation, a
failure to feel fetal movements or a uterus that is significantly smaller
than the expected size (31).
3.3.2 Medical management of IUFD at ≥ 14 to ≤ 28 weeks of gestation: Recommendation 2IUFD may be managed expectantly, or treated surgically or medically.
The decision about the mode of management of IUFD should be based
upon the individual’s clinical condition and preference for treatment.
Medical management of IUFD includes the use of mifepristone
in combination with misoprostol (recommended) or misoprostol
alone (alternate).
3.3.3 Evidence summary and rationale for Recommendation 2 A systematic review assessed the effectiveness, safety and acceptability
of misoprostol treatment of IUFD at ≥ 14 to ≤ 28 weeks of gestation (32).
A total of 16 RCTs were identified for inclusion in the review. Studies
were included in the review if they included cases of IUFD at ≥ 14 to
≤ 28 weeks and if these cases were evenly distributed between the
study arms. Studies that included IUFD at < 14 weeks or > 28 weeks
of gestation were considered only if the mean gestational age of
participants was within the range of ≥ 14 to ≤ 28 weeks.
The review included studies that compared regimens of mifepristone
used in combination with misoprostol versus misoprostol alone, as well as
those that compared different doses of misoprostol after administration
of mifepristone, different doses of misoprostol with or without a loading
dose, different routes of administration of misoprostol and different
preparations of misoprostol (i.e. moistened or dry).
Effects (benefits and harms) The reviewed studies showed that women treated with a combination
of mifepristone and misoprostol had higher rates of complete
abortion within 24 hours and a shorter expulsion time than those
treated with misoprostol alone. For both combination regimens and
misoprostol-only regimens, women treated with 400 μg misoprostol
had higher rates of complete abortion within 24 hours and lower
rates of serious adverse events than women treated with alternative
dosages of misoprostol. In the studies that compared routes of
21
RECOMMENDATIONSCOMBINATION REGIMEN
(RECOMMENDEDª)
MISOPROSTOL-ONLY
(ALTERNATE)
MIFEPRISTONE MISOPROSTOL MISOPROSTOL
INTRAUTERINE FETAL DEMISE
≥ 14–28 WEEKS200 mg PO once
400 μg PV or SL
every 4–6 hoursb
400 μg SL (preferred) or PV every 4–6 hoursb
a Combinat ion regimen is recommended because i t is more effect ive.
b Repeat doses of misoprostol can be considered when needed to achieve success of the abort ion process. In this guidel ine we do not provide a maximum number of doses of misoprostol . Health-care providers should use caut ion and c l in ical judgement to decide the maximum number of doses of misoprostol in pregnant indiv iduals with pr ior uter ine incis ion. Uter ine rupture is a rare compl icat ion; c l in ical judgement and health system preparedness for emergency management of uter ine rupture must be considered with advanced gestat ional age.
1–2 DAYS
RECOMMENDATION 2Medical management for intrauterine fetal demise at ≥ 14 to ≤ 28 weeks of gestation 7
PO: oral ; PV: vaginal ; SL: subl ingual
We suggest the use of 200 mg mifepristone administered orally, followed 1–2 days later by repeat doses of 400 μg misoprostol administered sublingually or vaginally every 4–6 hours.b The minimum recommended interval between use of mifepristone and misoprostol is 24 hours.
For the misoprostol-only regimen, we suggest the use of repeat doses of 400 μg misoprostol administered sublingually every 4–6 hours.b
Where sublingual misoprostol is not used, we suggest the use of repeat doses of 400 μg misoprostol administered vaginally every 4–6 hours.b
Notes: • Data related to gestational ages over 24 weeks of gestation were more l imited.
• The use of a loading dose of misoprostol is not necessary. There is no advantage to the use of moistened over dry misoprostol.
RECOMMENDATION TYPE: NEW OR UPDATED
Recommendation 2 is new.
7 In this guideline, duration of pregnancy (gestation) is the size of the uterus, estimated in weeks, based on clinical examination, that corresponds to a pregnant uterus of the same gestational age dated by last menstrual period (LMP).
administration for misoprostol, there was no strong evidence of one
route being superior to another.
Values We were not able to identify research addressing the value placed
on management of IUFD. Generally, we made the assumption that
individuals would value shorter induction to expulsion times, and
would value avoiding additional surgical intervention, serious adverse
events and minor side-effects. However, there may be important
variability in how much individuals value these outcomes, particularly
in relation to each other. For example, a person may choose a longer
induction to expulsion time if it is associated with a lower risk of
serious adverse events and minor side-effects.
22
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sEquity We were unable to identify research on aspects of equity related to the
relative effectiveness of the intervention in different subgroups; no
assumptions were made.
Resources We were unable to identify research that explored the costs involved or
the cost-effectiveness of the intervention among the studies included
in the systematic review. However, serious adverse events related to
medical management of IUFD are rare. In cases where additional hospital
resources are required, such as blood transfusion, inpatient management
or analgesic measures, we assume that the costs associated with this care
will be higher. We were unable to determine the impact that the use of
mifepristone has on costs. While there may be an increased upfront cost
in the delivery of a combination regimen (mifepristone and misoprostol),
the overall resource use (and cost) may be decreased due to a shorter
abortion process and higher success rates.
Acceptability Several factors impacting acceptability were considered in the
development of this recommendation, including tolerability of
medication. Overall, women were satisfied with their treatment
(33–35) and found the pain associated with the induction less than or
the same as they expected (35).
Feasibility We were unable to identify research on the feasibility of implementing
the use of misoprostol alone or in combination with mifepristone for
the management of IUFD at ≥ 14 to ≤ 28 weeks specifically. However,
the 16 studies were conducted across 17 countries (one study was
conducted across sites in two countries) providing information on the
varying country contexts in which such services may be provided. Of
these 17 countries, six were lower-middle-income economies, seven
were upper-middle-income economies and four were high-income
economies (32).
Rationale for Recommendation 2: Women treated with a
combination of mifepristone and misoprostol had higher rates of
successful abortion within 24 hours and a shorter expulsion time
than those treated with misoprostol alone. The certainty of the
evidence ranged from low to very low. Evidence suggests that in
both combination regimens and misoprostol-only regimens, the use
of 400 μg misoprostol leads to higher rates of successful abortion
within 24 hours and lower rates of serious adverse events compared
with other doses.
3.3.4 Additional considerations For the health-care providers managing IUFD at ≥ 14 to ≤ 28 weeks of
gestation, the recommendations for cadres who can manage medical
abortion at > 12 weeks can be followed. Alongside non-specialist
and specialist doctors, additional cadres – including nurses, midwives
and associate/advanced associate clinicians – can provide care
23
where there is access to appropriate surgical backup and the proper
infrastructure is available to address incomplete abortion or other
complications (10). Patient preference should be considered when
determining the route of misoprostol administration in medical
management.
3.3.5 Research gapsGeneral:
Identification of the most effective medical regimen for IUFD
management is needed. In particular, future research can
investigate the efficacy of lower doses of misoprostol, such as
200 μg, when used with mifepristone.
Misoprostol dosage for management of IUFD at < 20 weeks
versus 20–28 weeks of gestation should be investigated.
24
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s
RECOMMENDATIONSCOMBINATION REGIMEN
(RECOMMENDEDª)
MISOPROSTOL-ONLY
(ALTERNATE)
MIFEPRISTONE MISOPROSTOL MISOPROSTOL
INDUCED ABORTION
< 12 WEEKS200 mg PO once
800 μg B, PV or SLb,c
800 μg B, PV or SLb,c
a Combinat ion regimen is recommended because i t is more effect ive.
b Considerat ion for pat ient and provider preference suggests the inclusion of a l l routes, inc luding buccal administrat ion.
c See note on next page ( for Recommendation 3b).
1–2 DAYS
RECOMMENDATION 3AMedical management of induced abortion at < 12 weeks of gestation8
B: buccal ; PO: oral ; PV: vaginal ; SL: subl ingual
We recommend the use of 200 mg mifepristone administered orally, followed 1–2 days later by 800 μg misoprostol administered vaginally, sublingually or buccally.b,c The minimum recommended interval between use of mifepristone and misoprostol is 24 hours.
For the misoprostol-only regimen, we recommend the use of 800 μg misoprostol administered vaginally, sublingually or buccally.b,c
Notes: • There is l imited evidence to suggest that simultaneous dosing of mifepristone and misoprostol is
efficacious (39,40).
RECOMMENDATION TYPE: NEW OR UPDATED
Recommendation 3a has been updated from the WHO 2012 Safe abortion guidance (6). This updated recommendation applies to pregnancies up to 12 weeks of gestation, whereas in the prior guidance, different regimens were recommended for pregnancies up to 7 weeks, 9 weeks and 12 weeks. For the recommended misoprostol-only regimen, buccal route of administration has been added and the maximum number of doses has been removed. Interval dosing has been removed and a note has been added that repeat doses of misoprostol can be considered to achieve success of the abortion process.
8 In this guideline, duration of pregnancy (gestation) is the size of the uterus, estimated in weeks, based on clinical examination, that corresponds to a pregnant uterus of the same gestational age dated by last menstrual period (LMP).
3.4 Induced abortion
3.4.1 Indication for induced abortionPeople with an unplanned, mistimed or unwanted pregnancy may
choose to have a medical abortion. Medical abortion refers to the
sequential use of mifepristone followed by misoprostol or, in settings
where mifepristone is not available, the use of misoprostol alone,
to induce abortion, as an alternative to surgical management of
abortion. An enabling regulatory and policy environment is needed
to ensure that every individual who can become pregnant and who
is legally eligible has ready access to safe abortion care. Laws and
policies on abortion should protect health and human rights (6).
25
RECOMMENDATIONSCOMBINATION REGIMEN
(RECOMMENDEDª)
MISOPROSTOL-ONLY
(ALTERNATE)
MIFEPRISTONE MISOPROSTOL MISOPROSTOL
INDUCED ABORTION ≥ 12 WEEKS
200 mg PO once
400 μg B, PV or SL
every 3 hoursb,c
400 μg B, PV or SL
every 3 hoursb,c
a Combinat ion regimen is recommended because i t is more effect ive.
b Evidence suggests that vaginal route is the most effect ive. Considerat ion for pat ient and provider preference suggests the inclusion of a l l routes, inc luding buccal administrat ion.
c Repeat doses of misoprostol can be considered when needed to achieve success of the abort ion process. In this guidel ine we do not provide a maximum number of doses of misoprostol . Health-care providers should use caut ion and c l in ical judgement to decide the maximum number of doses of misoprostol in pregnant indiv iduals with pr ior uter ine incis ion. Uter ine rupture is a rare compl icat ion; c l in ical judgement and health system preparedness for emergency management of uter ine rupture must be considered with advanced gestat ional age.
1–2 DAYS
RECOMMENDATION 3BMedical management of induced abortion at ≥ 12 weeks of gestation
B: buccal ; PO: oral ; PV: vaginal ; SL: subl ingual
We suggest the use of 200 mg mifepristone administered orally, followed 1–2 days later by repeat doses of 400 μg misoprostol administered vaginally, sublingually or buccally every 3 hours.b,c The minimum recommended interval between use of mifepristone and misoprostol is 24 hours.
For the misoprostol-only regimen, we suggest the use of repeat doses of 400 μg misoprostol administered vaginally, sublingually or buccally every 3 hours.b,c
Notes: • The use of a loading dose of misoprostol is not necessary. There is no advantage to the use of
moistened over dry misoprostol.
RECOMMENDATION TYPE: NEW OR UPDATED
Recommendation 3b has been updated from the WHO 2012 Safe abortion guidance (6). For this recommendation, the combination regimen (mifepristone and misoprostol) does not have the loading dose of 800 μg misoprostol as in the prior guidance. For both the combination regimen and the misoprostol-only regimen, the buccal route has been added as an option. Maximum number of doses has been removed and the time period between mifepristone and misoprostol dosing is given in days.
3.4.2 Medical management of induced abortion: Recommendations 3a and 3bThe decision about abortion management should be based on the individual’s
preference for treatment. The WHO guideline, Safe abortion: technical and
policy guidance for health systems (2012), recommends manual or electric
vacuum aspiration, dilation and evacuation, or medical management, either
using a combination regimen (mifepristone followed by misoprostol) or
misoprostol alone (6). Mifepristone followed by a prostaglandin analogue
has been shown to be safe and effective (36). Limited evidence also suggests
that a regimen with repeated doses of misoprostol between 9 and 12 weeks
of gestation is safe and effective (4,28,37,38); however, use of misoprostol
alone is less effective than its use in combination with mifepristone.
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sThis guideline provides updated information related to specific
dosages, routes and regimens for medical abortion, which differ for
pregnancies of different gestational ages.
3.4.3 Evidence summary and rationale for Recommendations 3a and 3bThree systematic reviews served as the evidence base for the
effectiveness, safety and acceptability of medical management of
induced abortion regimens using mifepristone plus misoprostol (the
combination regimen) or misoprostol alone: the first was for induced
abortions at ≤ 63 days of gestation (41); the second was for induced
abortions at > 63 days and up to 84 days (42); and the third was for
induced abortions at ≥ 12 weeks of gestation (43).
In the first systematic review, 41 studies were included towards the
development of this recommendation comparing the combination
regimen to the use of misoprostol alone, and comparing
different routes, doses and dosing intervals for misoprostol after
administration of mifepristone, and different doses of misoprostol in
misoprostol-only regimens (41).
In the second systematic review, five studies were included towards the
development of these recommendations comparing different routes
of misoprostol administration after use of mifepristone, different
doses of misoprostol administration in misoprostol-only regimens, and
comparing the management of induced abortion in a health-care facility
to self-management by the pregnant individual (42).
In the third systematic review, a total of 44 RCTs were identified for
inclusion. The review included studies that compared the combination
regimen with misoprostol alone. Studies also compared different
doses of misoprostol after administration of mifepristone, different
doses of misoprostol with or without a loading dose, different routes
of administration of misoprostol, and different preparations of
misoprostol (i.e. moistened or dry) (43).
Effects (benefits and harms) The first review, on induced abortions at ≤ 63 days of gestation (41),
revealed that the combination regimen had higher rates of successful
abortion and lower rates of ongoing pregnancy than the misoprostol-
only regimen. In the studies comparing misoprostol doses and interval
of misoprostol administration in the combination regimen, there were
higher rates of successful abortion and lower rates of ongoing pregnancy
with 800 μg of misoprostol and an interval of at least 24 hours between
use of mifepristone and misoprostol. Studies comparing the different
routes of misoprostol administration revealed the vaginal and sublingual
routes to be more effective. In the few studies that compared misoprostol
dosages in misoprostol-only regimen, 800 μg of misoprostol had lower
rates of ongoing pregnancy and higher rates of successful abortion.
27
The second systematic review revealed that medical abortion is effective
in the late first trimester (> 63 days and up to 84 days of gestation) (42).
A combination regimen is significantly more effective than a
misoprostol-only regimen. Success rates were higher with repeat dosing
of misoprostol both in combination regimens and when misoprostol
was used alone, and they were also higher with vaginal rather than
oral administration for repeat dosing. Two studies addressed outpatient
medical abortion, showing no significant difference in effectiveness,
safety or acceptability between the two groups.
The third systematic review, on induced abortion at ≥ 12 weeks,
showed that combination regimens had lower rates of ongoing
pregnancy at 24 and 48 hours when compared with misoprostol-only
regimens. Dosing of mifepristone 24 hours before misoprostol had
lower rates of ongoing pregnancy when compared to simultaneous
dosing of both medications. In misoprostol-only regimens, dosing
intervals of 3 hours had lower rates of ongoing pregnancy at 24 and
48 hours compared to other dosing intervals. For both combination
and misoprostol-only regimens, sublingual and vaginal misoprostol
routes of administration had better efficacy and lower rates of
side-effects than the oral route (43).
Values We were unable to identify research on values relating to the
management of medical abortion. We made the assumption that
individuals value outcomes of effectiveness and safety, but it is
unclear how they would value those outcomes when weighed against
side-effects and markers of acceptability.
Women may also strongly value certain interventions over others,
with preferences for route and timing of medication administration,
and type of intervention (medical or surgical) differing significantly
between one woman and another, or one region of the world and
another (44–46). Consideration should also be given to the value
women place on the timing and cost of abortion services as well as
opportunities to take part in managing their own abortion care in
situations where at-home dosing or abortion self-management are
available (47–49).
Equity We were unable to identify research on aspects of equity around
relative effectiveness of the interventions in different subgroups.
However, in 4 studies, participants ranged in age from 16 to 44 years,
demonstrating inclusion of people across age groups (50–53).
Resources In the studies included in the three systematic reviews, we were
unable to identify research that explored the costs involved or the
cost-effectiveness. Studies on medical abortion include analgesic
options ranging from oral to parenteral administration, including
opiates, depending on gestational age. In cases where additional
An enabling regulatory and policy environment is needed to ensure that every individual who can become pregnant and who is legally eligible has ready access to safe abortion care.
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shospital resources are required, such as blood transfusion, inpatient
management, analgesic measures or foeticide, we assume that the
costs associated with these services will be higher. We were unable to
determine the impact that the use of mifepristone has on costs. While
there may be an increased upfront cost with the use of a combination
regimen, the overall resources used may be decreased due to a shorter
abortion process and a higher success rate.
Feasibility We were unable to identify research on the feasibility of implementing
the use of misoprostol alone or in combination with mifepristone
for the management of medical abortion. However, four studies
conducted in women with pregnancies 9–12 weeks of gestation
reported that the medical abortion service was provided as outpatient
care indicating feasibility of offering the service through outpatient
health-care facilities (33,50,51,53). Additionally, studies related to
management of medical abortion at < 12 weeks of gestation were
conducted across 10 countries: two high-income, three upper-middle-
income, four lower-middle-income and one low-income economy (41).
Studies related to management of medical abortion at ≥ 12 weeks
of gestation were conducted across 23 countries (four studies were
conducted across sites in multiple countries): one was a low-income
economy, six were lower-middle-income economies, five were upper-
middle-income economies, and 11 were high-income economies (43).
Acceptability Generally, women find various routes of misoprostol administration
acceptable (48,49,54–59). Additionally, women found the side-effects
to be acceptable (47,49). Women receiving care for management of
medical abortion at < 12 weeks of gestation reported that the ability
to predict timing of the bleeding was the best feature of taking the
medicines at home (51). Home use of medical abortion at < 12 weeks
gestation following an interaction with a health-care provider enabled
women to keep working or reduced opportunity costs (51).
Rationale for Recommendation 3a (on medical abortion at
< 12 weeks of gestation): The combination mifepristone and
misoprostol regimen is based on moderate certainty of evidence
for induced abortion at < 12 weeks. In combination regimens,
misoprostol dosage of 800 μg administered vaginally, sublingually or
buccally is recommended based on moderate certainty of evidence.
Evidence is limited regarding the use of misoprostol-only regimens,
especially between 9 and 12 weeks of gestation. Thus, the GDG
members took the view that when using misoprostol-only regimens,
the dose of 800 μg administered vaginally, sublingually or buccally is
safe, effective and acceptable.
Rationale for Recommendation 3b (on medical abortion at ≥ 12
weeks of gestation): The combination mifepristone and misoprostol
regimen is based on moderate certainty of evidence for induced
Women receiving care for
management of medical
abortion at < 12 weeks of
gestation reported that the
ability to predict timing
of the bleeding was the
best feature of taking the
medicines at home (51).
29
abortion at ≥ 12 weeks. Mifepristone 200 mg is suggested based on
success, women’s values and cost (given the higher price of 600 mg
of mifepristone) based on low to very low certainty of evidence.
Misoprostol dosage of 400 μg administered every 3 hours is suggested
based on overall very low certainty of evidence and is conditional
upon resources available in different settings. Evidence on use of
the buccal route was inconclusive, but it should be considered as an
acceptable option if an individual prefers this route of administration.
This is based on low to very low certainty of evidence.
3.4.4 Additional considerationsGiven the nature of the medical abortion process when using the
combination regimen, it is possible for individuals to play a role in
managing some of the components by themselves outside of a health-care
facility. Where there is access to a source of accurate information and to
a health-care provider (should one be needed or wanted at any stage of
the process), the abortion process can be self-managed with pregnancies
< 12 weeks of gestation without the direct supervision of a health-care
provider (10) (evidence is limited for pregnancies > 10 weeks [53,60–64]).
For provision of medical abortion of pregnancies < 12 weeks, the
following cadres have been recommended: auxiliary nurses, auxiliary
nurse midwives, nurses, midwives, associate/advanced associate clinicians,
and non-specialist and specialist doctors. Doctors of complementary
systems of medicine can be providers of this service in health system
contexts with an established mechanism for the participation of such
doctors in other tasks related to maternal and reproductive health (10).
Alongside non-specialist and specialist doctors, the following cadres can
provide medical abortion for pregnancies ≥ 12 weeks in contexts where
appropriate surgical backup and proper infrastructure is established and
easily accessible to address incomplete abortion or other complications:
nurses, midwives, associate/advanced associate clinicians (10).
3.4.5 Research gapsGeneral:
The various next steps that individuals can take, if needed, after
medical abortion should be further evaluated. This includes
self-assessment of the success of medical abortion, in particular
for misoprostol-only regimens, which tend to be used in more
restrictive settings and which are less effective.
For those with uterine scars, the safety and efficacy of medical
abortion regimens is an area requiring more research. In particular,
the misoprostol dosage when used in combination with mifepristone
and when used in misoprostol-only regimens for pregnancies 13–20
weeks versus 20–28 weeks of gestation can be investigated.
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s Additional evidence is needed on the cost-effectiveness of all
medical abortion interventions.
Qualitative research is needed on individuals’ values and
preferences relating to all medical abortion interventions.
Medical abortion at < 12 weeks of gestation:
Studies are needed on the efficacy, safety and acceptability of
medical abortion (combination mifepristone and misoprostol
regimens and misoprostol-only regimens) in the outpatient setting
for pregnancies 9–12 weeks of gestation. This includes the follow-
up care for medical abortion when self-assessment is used to
determine eligibility for and success of the medical abortion.
Medical abortion at ≥ 12 weeks of gestation:
Studies are needed to determine the gestational age limit within
which it is safe to carry out medical abortion without hospital
admission.
In connection to the research gap noted above, qualitative research will
also be needed on the acceptability of outpatient medical abortion.
31
3.5 Post-abortion contraception
3.5.1 Provision of post-abortion contraceptionContraception can be initiated at the time of administration of the
first pill of the medical abortion regimen or after assessment of
successful medical abortion. All contraceptive options may be used.
Criteria laid out in the WHO publications Medical eligibility criteria
for contraceptive use and Ensuring human rights in the provision of
contraceptive information and services should be adhered to (65,66).
CONTRACEPTIVE METHOD
POST-ABORTION CONDITION
FIRST
TRIMESTER
SECOND
TRIMESTER
IMMEDIATE
POST-SEPTIC
ABORTION
COMBINED ORAL CONTRACEPTIVES (COCS ) 1 1 1
COMBINED INJECTABLE CONTRACEPTIVES (CICS ) 1 1 1
PATCH & VAGINAL RING 1 1 1
PROGESTERONE-ONLY PILLS (POPS ) 1 1 1
PROGESTOGEN-ONLY INJECTABLES: DMPA, NET-EN (depot medroxyprogesterone acetate, norethisterone enanthate)
1 1 1
PROGESTOGEN-ONLY IMPLANTS: LNG, ETG ( levonorgestrel, etonogestrel)
1 1 1
COPPER-BEARING INTRAUTERINE DEVICE ( IUD) 1 2 4
LNG-RELEASING IUD 1 2 4
CONDOMS 1 1 1
SPERMICIDE 1 1 1
DIAPHRAGM 1 1 1
DEFINITION OF CATEGORIES
1. A condition for which there is no restriction for the use of the contraceptive method.
2. A condition where the advantages of using the method generally outweigh the theoretical or proven risks.
3. A condition where the theoretical or proven risks usually outweigh the advantages of using the method.
4. A condition that represents an unacceptable health risk if the contraceptive method is used.
Source: WHO (2015) (65)
TABLE 3Post-abortion medical eligibility recommendations for contraceptive methods
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s
TIMING OF POST-ABORTION CONTRACEPTION
IMMEDIATE INITIATION
HORMONAL CONTRACEPTION Immediately after the first pill of the medical abortion
RECOMMENDATION 4ATiming of post-abortion hormonal contraception initiation, except for intrauterine device (IUD)
For individuals undergoing medical abortion with the combination mifepristone and misoprostol regimen or the misoprostol-only regimen who desire hormonal contraception (oral contraceptive pills, contraceptive patch, contraceptive ring, contraceptive implant or contraceptive injections), we suggest that they be given the option of starting hormonal contraception immediately after the first pill of the medical abortion regimen.
Notes: • All individuals who can become pregnant should be provided with all of the necessary information to
make an informed decision regarding the use of contraception. Immediate initiation of intramuscular (IM) depot medroxyprogesterone acetate (DMPA) is associated with a slight decrease in the effectiveness of medical abortion regimens (67). However, immediate initiation of DMPA should still be offered as an available contraceptive method after an abortion.
• Indirect evidence was used as a basis for decision-making on initiation of hormonal contraception as an option for individuals undergoing medical abortion with misoprostol alone.
• No data were available on the use of combined hormonal contraception (pills or injections) by those undergoing medical abortion.
RECOMMENDATION TYPE: NEW OR UPDATED
Recommendation 4a is a new recommendation.
3.5.2 Timing of post-abortion contraception: Recommendations 4a and 4bThe following recommendations provide further clarification on the
timing of initiating contraception after a medical abortion.
3.5.3 Evidence summary and rationale for Recommendations 4a and 4bThree systematic reviews served as the evidence base for the
timing of post-abortion contraception. The first systematic review
assessed the efficacy and safety of non-IUD hormonal contraception
initiation after abortion (including medical abortion) (68). Three
RCTs (67,69,70) and one cohort study (71) compared immediate
versus delayed initiation of implants or DMPA after medical
abortion with mifepristone and misoprostol. No studies assessed
hormonal contraception initiation after medical abortion with a
misoprostol-only regimen.
33
TIMING OF POST-ABORTION CONTRACEPTION
IMMEDIATE INITIATION
IUD With assessment of successful abortion
RECOMMENDATION 4BTiming of post-abortion intrauterine device (IUD) placement
For individuals undergoing medical abortion with the combination mifepristone and misoprostol regimen or the misoprostol-only regimen who wish to have an IUD inserted, we suggest IUD placement at the time that success of the abortion procedure is determined. The use of clinical signs with bimanual examination, serum human chorionic gonadotrophin (hCG) levels or ultrasonography (if available), and an assessment of the individual’s current symptoms can be used to determine whether or not there is an ongoing pregnancy.
RECOMMENDATION TYPE: NEW OR UPDATED
Recommendation 4b is a new recommendation.
The second systematic review assessed contraceptive continuation at six
months (implants, DMPA and IUD) and unintended pregnancies after the
index abortion (72). This review included the same three RCTs (67,69,70)
and one cohort study (71) that were included in the first review.
The third systematic review assessed the effectiveness and safety of
initiation of IUD after abortion (73). In this review, three studies compared
immediate versus delayed IUD insertion after medical abortion with
mifepristone and misoprostol (74–76). The included studies assessed
copper-bearing and levonorgestrel-releasing IUDs. No studies assessed
IUD initiation after medical abortion with a misoprostol-only regimen.
Effects (benefits and harms) The findings of the three RCTs and one cohort study in the first
systematic review (68) showed that there was little difference in the
rates of successful abortion between the two groups (immediate
versus delayed initiation of implants or DMPA after medical abortion)
and satisfaction regarding the timing of their contraception initiation
was high. Findings from the same studies, which were also reviewed
in the second systematic review (72), showed that continuation rates
at six months were higher for the women in the immediate initiation
group. Contraceptive failure rates were lower among women who
initiated the implant, DMPA or the IUD immediately. The studies on
immediate versus delayed IUD insertion after medical abortion in the
third systematic review (73) showed that there was no difference
between the immediate and delayed insertion groups with regard
to adverse events or the need for further intervention after IUD
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splacement. There were fewer expulsions of the IUD at 12 months
among women who had undergone immediate IUD placement.
Values Women placed high value on accepting a contraceptive method to
prevent a future pregnancy. Two studies looking at DMPA and
implants reported that women undergoing an abortion placed high
importance on preventing a pregnancy in the next six months (67,70).
Resources In regard to resource requirements and cost-effectiveness, there was
no direct research evidence that explored these domains. The cost
of the IUD and implant versus pills and injections in various country
contexts could not be determined. While there may be increased
upfront costs of the IUD and implant, related to the cost of the
devices, provider training and additional placement and removal
visits, costs may decrease over time compared with the repeated
need for pills and injections (77).
Equity There was no research evidence identified on aspects of equity around
the relative effectiveness of the intervention in different subgroups.
However, three studies included adolescents (67,70,71) and three
studies included nulliparous women (74–76).
Acceptability Women reported high satisfaction with immediate initiation of their
implant or DMPA administration (67,70). Acceptability and satisfaction
were also reported by women in the immediate-start group based
on fewer visits made to the health-care provider compared with the
delayed-start group (70). Immediate initiators of implants had higher
attendance at follow-up appointments (69,71).
For the IUD studies, similar considerations were taken into account.
None of the included studies specifically addressed acceptability of
the service to women. However, timing of insertion can be used as a
proxy indicator for acceptability; more women had the IUD placed at
the time that successful abortion was determined compared with the
number of women who opted for delayed insertion (74,76). The rate
of loss to follow-up at six months was reportedly lower for the ear-
ly-insertion group as compared with the delayed insertion group (75).
Feasibility Initiation of post-abortion contraception appears feasible to implement.
The included studies for both IUD and hormonal contraception were
conducted through outpatient clinics, indicating feasibility of offering
the service through outpatient health-care facilities.
35
Rationale for Recommendation 4a (on post-abortion hormonal
contraception initiation, except for IUD): There was little
difference in the successful abortion rates between women who
started non-IUD hormonal contraception after receiving mifepristone
versus those who started after receiving both mifepristone and
misoprostol. This difference was based on low certainty of evidence.
Women placed value on accepting a contraceptive method and they
placed value on preventing future pregnancies. Satisfaction with and
acceptability of immediate initiation of a contraceptive method was
high. Continuation rates for the implant at six months were higher
for the women in the immediate-initiation group. The certainty of the
evidence was very low.
Rationale for Recommendation 4b (on post-abortion IUD
placement): Placement of an IUD at the time the abortion process has
been deemed successful leads to lower rates of contraceptive failure
and higher continuation rates at 6 and 12 months. The 6-month
continuation rates are based on moderate certainty of evidence while
the contraceptive failure rates are based on low certainty of evidence
and the continuation rates at 12 months are based on very low
certainty of evidence. There is no difference in the number of women
requiring further intervention post-IUD placement due to retained
tissue or bleeding, but the certainty of the evidence was low. There
is no difference in the side-effect of pain at IUD insertion between
the two groups, based on moderate certainty of evidence. Serious
adverse events are rare and there was no difference between the two
groups for uterine perforation or death, but this was based on very
low certainty of evidence. Acceptability and feasibility of immediate
placement of the IUD was high.
3.5.4 Additional considerationsAll individuals who can become pregnant should be informed that
ovulation can return within two weeks following abortion, putting
them at risk of pregnancy unless an effective contraceptive method is
used. Those who are interested in contraception should be provided
with accurate information to assist them with choosing the most
appropriate contraceptive method to meet their needs. Some prefer
to discuss options for contraception after the abortion is completed.
For those seeking an abortion following a reported contraceptive
failure, it is important to discuss whether the method may have been
used incorrectly and how to use it correctly, or whether it may be
appropriate to change to a different method. Ultimately, the final
decision about whether to use contraception, and which method to
use, is up to the individual alone (19).
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sIMPORTANT NOTE: Acceptance of a contraceptive method must
never be a precondition for providing an abortion.
For the health workforce, task sharing guidelines have offered options
for various cadres to conduct different aspects of the provision of
contraception counselling and services (10,78).
For injectable contraception administration, the following cadres
have been recommended: auxiliary nurses, auxiliary nurse midwives,
nurses, midwives, pharmacists, associate/advanced associate clinicians,
and non-specialist and specialist doctors. Doctors of complementary
systems of medicine can be providers of this service in health system
contexts with an established mechanism for the participation of such
doctors in other tasks related to maternal and reproductive health.
Pharmacy workers can administer the injectable contraceptive under
direct supervision of a pharmacist. Lay health works as administrators
of injectable contraception can be an option if conducted under
targeted monitoring and evaluation (10).
For implant insertion and removal, the following cadres have been
recommended: nurses, midwives, pharmacists, associate/advanced
associate clinicians, and non-specialist and specialist doctors. Auxiliary
nurses and auxiliary nurse midwives may perform implant insertion/
removal within the context of targeted monitoring and evaluation.
Doctors of complementary systems of medicine can be providers of
this service in health system contexts with an established mechanism
for the participation of such doctors in other tasks related to maternal
and reproductive health and where training in implant removal is
given along with training in insertion (10).
For IUD placement, the following cadres have been recommended:
auxiliary nurse midwives, nurses, midwives, associate and advanced
associate clinicians, non-specialist and specialist doctors. Doctors of
complementary systems of medicine can be providers of this service
in health system contexts with an established mechanism for the
participation of such doctors in other tasks related to maternal and
reproductive health (10).
Self-administration of injectable contraception is an option in contexts
where mechanisms to provide appropriate information and training
exist, referral linkages to health-care providers are strong, and
monitoring and follow-up can be ensured (10).
37
3.5.5 Research gapsGeneral:
Studies are needed on the efficacy, safety and acceptability of
immediate initiation of contraception with misoprostol-only
regimens.
Studies on the efficacy, safety and acceptability of the initiation
of combined hormonal contraception at the time of mifepristone
administration are also lacking.
Recommendations on the timing of post-abortion contraception
are inclusive of combined hormonal contraception and
misoprostol-only regimens, based on indirect evidence. Results
from the survey on research gaps (completed by GDG members)
noted the lack of direct evidence for these clinical scenarios and,
therefore, further research on this topic should be pursued.
38
4. General implementation considerations
39
General implementation considerations for the recommendations in this
guideline are outlined below through a question-and-answer format.
IMPORTANT NOTE: The quality of medicines used is an important
factor that can influence the process and overall success of a
medical abortion. Substandard mifepristone and/or misoprostol
products that do not contain the right active ingredients in the
right dosages, and those that are not manufactured, transported or
stored under the specified conditions, can affect the outcomes of
a medical abortion. It is critical that mifepristone and misoprostol
used for medical abortion are properly manufactured in line with
specifications and are handled appropriately through the supply
chain until use at the point of care. Ensuring use of quality-assured
mifepristone and misoprostol that has been transported and stored
correctly according to the specified conditions can contribute to the
overall quality of a medical abortion process.
Q: Where should medical abortion services be available?
A: Services should be available at the primary-care level, with referral
systems in place for all required higher-level care.
Q: Who can provide these medical abortion services?
A: In addition to non-specialist doctors and specialist doctors, with
task-specific training and functioning systems for monitoring and
supportive supervision, a wide range of health worker cadres
– such as auxiliary nurses, auxiliary nurse midwives, nurses,
midwives, associate/advanced associate clinicians, pharmacists and
40
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n doctors of complementary medicine – can provide various aspects
of medical abortion services. In addition, indirect evidence from a
qualitative systematic review on factors affecting implementation
of task sharing in abortion identified that some providers in
a middle-income setting where abortion is legal saw medical
abortion as having a number of benefits for health services (9).
These reported benefits included that it was safe and effective;
it would reduce the burden on health services; and it may make
it easier for people involved to act in accordance with their
conscience. A discussion of general considerations for task shifting
in maternal health and family planning can be found in the 2012
OptimizeMNH guideline: WHO recommendations: optimizing
health worker roles to improve access to key maternal and
newborn health interventions through task shifting (78).
The specific cadres able to provide medical abortion services have
been outlined in the additional considerations section for each
recommendation.
Q: Can medical abortion processes be self-managed?
A: When using the combination mifepristone and misoprostol
regimen, the medical abortion process can be self-managed for
pregnancies up to 12 weeks of gestation, including the ability
to take the medications at home, without direct supervision of a
health-care provider (10); it should be noted that there was limited
evidence for pregnancies beyond 10 weeks (53,60–64). This is
an option in circumstances where individuals have a source of
accurate information and access to a health-care provider should
they need or want it at any stage during the process (10).
Q: What general considerations should be taken into account
when providing care to adolescents/youth?
A: Ensure that you are fully aware of the national and local laws and
policies. In your work with adolescents, you may find that in some
situations, prevailing laws and policies may not permit you to do what
is in the best interests of your adolescent patient (e.g. in some places,
the provision of contraceptives to unmarried adolescents is illegal). In
such situations, you may need to draw upon your experience and the
support of caring and knowledgeable people to find the best way to
balance your legal obligations with your ethical obligations (13).
Provide information on the implications of each treatment option
and help the adolescent choose the one best suited to his/her
needs. While doing this:
present all the relevant information;
respond to questions as fully and honestly as you can;
41
help them choose; and
respect their choice, even if it is not the one you would have
wanted them to make.
Adolescents may be reluctant to disclose information on sensitive
matters if their parents, guardians or spouses are also present.
Reduce the stigma around the issue by normalising it: an
adolescent who has an unwanted pregnancy or a sexually
transmitted infection may feel embarrassed or even ashamed.
You can reduce the stigma around the issue by saying to the
adolescent, “I have treated a number of young people with the
same problem you have.”
Q: What considerations should be taken into account when
conducting a clinical interview and examination with
adolescents/youth?
A: Following is list of considerations and steps.
Respect local sensitivities regarding gender norms (e.g.
whether it is appropriate for a male health worker to examine
a female patient). If needed, ensure the presence of a female
colleague during the examination (13).
Ensure privacy (e.g. make sure that curtains are drawn, doors
are shut and that no unauthorized person enters the room
during the examination).
Start the clinical interview with issues that are the least
sensitive and least threatening; it is often best to ask first
about the activities of their peers and friends rather than
directly about their own activities.
If the adolescent is with an accompanying person, reach an
agreement as to whether they want this person to be present
during the examination.
Inform the adolescent about what examination you want to
carry out and the purpose of the examination.
Explain the nature of the examination.
Obtain the consent of the adolescent.
42
Imp
lem
enta
tio
n Q: How does one determine duration of pregnancy (gestation)?
A: Physical examination to assess uterine size (i.e. bimanual pelvic
and abdominal examination), assessment of last menstrual period
(LMP) and recognition of symptoms of pregnancy are usually
adequate. Laboratory or ultrasound testing may also be used,
if needed. Laboratory testing is needed when typical signs of
pregnancy are not clearly present and the provider is unsure
whether there is an ongoing pregnancy. Obtaining tests should
not hinder or delay uterine evacuation. Ultrasound scanning is
not routinely required. Where it is available, it can help identify an
intrauterine pregnancy and exclude an ectopic pregnancy (6,19).
Q: How can success of the medical abortion be determined?
A: Success of medical abortion is determined by signs and symptoms
as experienced by the individual. These may include heavy
bleeding with clots, passage of the products of conception, and
pain that may be significantly stronger than normal menstrual
cramps. If ongoing symptoms of pregnancy are reported and/or there
has only been minimal or no bleeding after taking the medications
as directed, ongoing pregnancy should be suspected and further
evaluation could include pelvic examination (demonstrating a
growing uterus) or an ultrasound scan (demonstrating an ongoing
pregnancy) (19).
Q: What is the role of ultrasound in these recommendations?
A: Ultrasound scanning is not routinely required for the provision
of abortion (6). Successful abortion may be confirmed by pelvic
examination, pelvic ultrasound or a repeat hCG measurement. If
serum hCG measurements are used, it should be remembered that
in some cases low hCG levels can be detectable for up to four
weeks after successful expulsion. Ultrasound is useful to detect
ongoing pregnancy by measuring endometrial thickness; it should
be noted, however, that endometrial thickness is not useful for
diagnosing incomplete abortion and its use as an indicator for this
purpose may lead to inappropriate surgical interventions (6).
For initiation of contraception, an ultrasound is not needed. Non-
IUD methods can be started immediately. IUDs can be inserted
whenever the medical abortion has been deemed successful (19).
Q: Is there a maximum number of doses of misoprostol that can
be used in the medical management of abortion?
A: Repeat doses of misoprostol can be considered when needed to
achieve success of the abortion process. In this guideline we do
not provide a maximum number of doses of misoprostol. Health-
care providers should use caution and clinical judgement to
decide the maximum number of doses of misoprostol in pregnant
individuals with prior uterine incision. Uterine rupture is a rare
43
complication; clinical judgement and health system preparedness
for emergency management of uterine rupture must be considered
with advanced gestational age.
Q: What is the best way to store misoprostol?
A: Aluminium blister packs are the best way to store misoprostol (79).
Cutting the blister pack and storing misoprostol outside the
aluminium blister may increase the risk of damage to the packaging
(i.e. the inner seal), leading to exposure to environmental
conditions (80).
Store misoprostol in dry conditions at temperatures at or below
25 °C (77 °F) (79,81).
Exposure to heat and humidity during manufacturing, packaging
and storage may compromise the quality of misoprostol (81).
Q: What is the best way to store mifepristone?
A: Store at 25 °C (77 °F); excursions permitted between 15 °
and 30 °C (59 ° and 86 °F) (82).
Q: When does return to ovulation occur after a medical abortion?
A: Ovulation can occur as few as eight days after a medical
abortion (83).
44
5. Dissemination and adaptation
6. Guideline impact evaluation and future updates
45
9 The webpage for this guideline, all language versions and related products is: http://www.who.int/reproductivehealth/publications/medical-management-abortion/en/ 10 Available at: www.who.int/rhl
Dissemination and adaptation
Translation of this guideline into Spanish (in collaboration with PAHO), French and Portuguese is planned.
Versions in other United Nations languages will be developed as needed. Third-party translations into
additional non-United Nations languages will be encouraged, provided they comply with WHO guidance
on such translations.
The digital versions of the guideline in all languages will be available via the WHO website9 and through the
WHO Reproductive Health Library (RHL) website.10 Print versions of this guideline will be distributed to WHO
regional and country offices, nongovernmental organization (NGO) partners, professional associations and other
networks and partners.
WHO regional offices are expected to be active partners in the dissemination and adaptation of these
guidelines. A number of other interested agencies and NGOs are encouraged to partner with WHO in the
dissemination and local adaptation of the guidelines and in developing derivative informational materials.
The guideline will be launched in WHO regions through regional dissemination meetings and specific
knowledge transfer and adaptation activities and implementation research will take place in select countries
based on need and interest to move ahead with implementation of the recommendations. Derivative products
will be developed, such as simple pocket-sized charts.
Guideline impact evaluation and future updates
Two years after publication of the guideline, an online survey will be conducted through WHO regional and
country offices and selected respondents representing other user groups (e.g. professional societies, NGOs).
The purpose of the survey will be to gauge in-country progress in utilization of the guideline, implementation of
the recommendations and any influence on policy decisions. It will also help in gathering feedback relevant to
future modifications of the guidance.
Evidence will be reviewed and the guideline updated in four years, or earlier if new evidence warrants an update.
46
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49
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50
ANNEX 1:
WHO staff and external experts involved in the guideline development process
51
* WHO/RHR is based at WHO headquarters, Geneva, Switzerland. Note: The Secretariat includes all members of the Steering Group who are affiliated with WHO/RHR (or were at the time of guideline development).
NAME & AFFILIATION
Ferid AbubekerMedical Officer, WHO Department of Reproductive Health and Research (WHO/RHR)*
Mavjuda BabamuradovaFormer Regional Acting Programme Manager, Sexual and Reproductive Health, WHO European Region
Bela GanatraScientist, WHO/RHR
Rodolfo GomezRegional Advisor, WHO Region of the Americas (Pan American Health Organization [PAHO])
A. Metin GülmezogluCoordinator, WHO/RHR
Caron KimMedical Officer, WHO/RHRResponsible Officer
Antonella Lavelanet Medical Officer, WHO/RHRResponsible Officer
Petrus SteynScientist, WHO/RHR
MEMBERS WHO Steering Group
52
NAME & AFFILIATION COUNTRY (WHO REGION) EXPERTISE COI*
GENDER
Josaphat K. Byamugisha M
Associate Professor, Makerere University, Department of Obstetrics and Gynecology, Mulago National Referral Hospital
Uganda
(African Region)
Clinical and reproductive health research
None
Laura Castleman F Medical Director, Ipas, Adjunct Clinical Assistant Professor, Department of Obstetrics and Gynecology, University of Michigan
United States of America
(Region of the Americas)
Reproductive health research and clinical care
None
Munir Kassa Eshetu M
Director for Reproductive Health Service Quality, Center for International Reproductive Health Training (CIRHT)
Ethiopia
(African Region)
Reproductive health None
Anibal Faúndes M
General Coordinator, International Federation of Gynecology and Obstetrics (FIGO) Initiative on Prevention of Unsafe Abortion
Brazil
(Region of the Americas)
Clinical care, obstetrics and gynaecology
None
Selma Hajri F Coordinator, African Network for Medical Abortion
Tunisia
(Eastern Mediterranean Region)
Women’s health, clinical and reproductive health research
None
Kirti Iyengar F Founder, Action Research & Training for Health (ARTH)
India
(South-East Asia Region)
Public health None
Hiromi Obara F Health Policy Advisor, Japan International Cooperation Agency (JICA)
Lao People’s Democratic Republic
(Western Pacific Region)
Clinical care, women’s health
None
Patricio Sanhueza M Head of Reproductive Health, Mexico City Secretariat of Health
Mexico
(Region of the Americas)
Public health, women’s health
None
Paul Van Look (CHAIR) M Independent consultant
Geneva
(European Region)
Sexual and reproductive health
None
Beverly Winikoff F
President, Gynuity Health Projects
United States of America
(Region of the Americas)
Clinical research, women’s health
None
Ann Yates F Midwifery Advisor, International Confederation of Midwives
The Netherlands
(European Region)
Clinical care, women’s health
None
GDG meeting observers
Jennifer Blum F Vice President, Programs and Strategic Initiatives, Gynuity Health Projects
United States of America
(Region of the Americas)
Clinical research on post-abortion care, medical abortion and postpartum haemorrhage
None
Kristina Gemzell-Danielsson F
Professor and Chair, Division of Obstetrics and Gynecology, Department of Women´s and Children´s Health, Karolinska Institutet
Sweden
(European Region)
Clinical research on contraception and abortion, guideline development
Declared
* Confl ict of interest (COI)
MEMBERS Guideline Development Group (GDG)
53
NAME & AFFILIATION EXPERTISE COI*
GENDER
Katie Alton F
Oregon Health & Science University
Abortion, family planning None
Ashley Brant F Medstar Washington Hospital Center
Abortion, family planning None
Amanda Cleeve F
Karolinska Institute
Abortion, family planning None
Kate Curtis F United States Centers for Disease Control and Prevention (CDC)
Public health, family planning None
Yokabed Ermias F United States Centers for Disease Control and Prevention (CDC)
Public health, family planning None
Roopan Gill F
University of British Columbia
Abortion, family planning None
Natalie Kapp F
Ipas
Abortion, family planning None
Caron Kim F
WHO Department of Reproductive Health and Research (WHO/RHR)
Abortion, family planning None
Jamie Krashin F CDC
Abortion, family planning None
Laura Laursen F
University of Chicago Medical Center
Abortion, family planning None
Antonella Lavelanet F
WHO/RHR
Abortion, family planning, policy None
Karthik Srinivasan M
Independent consultant
Abortion, family planning None
Katherine Whitehouse F
Independent consultant (former Medical Officer at WHO/RHR)
Abortion, family planning None
Guideline methodologists
Maria Rodriguez F Cochrane Fertility Regulation Group at Oregon Health & Science University
Quality appraisal using GRADE1 methodology, and translation of evidence into recommendations
None
Marita Sporstøl Fønhus F
Norwegian Knowledge Centre
Quality appraisal using GRADE1 methodology, and translation of evidence into recommendations
None
* Conflict of interest (COI) 1 GRADE: Grading of Recommendations Assessment, Development and Evaluation. Further information is available at: http://www.gradeworkinggroup.org/
MEMBERS Evidence Synthesis Team (EST)
54
NAME & AFFILIATION COUNTRY (WHO REGION) EXPERTISE COI*
GENDER
Sharon Cameron F
National Health Service (NHS) Lothian and Edinburgh University
United Kingdom
(European Region)
Medical abortion care None
Manju Chugani F
Rufaida College of Nursing
India
(South-East Asia Region)
Women’s health None
Guyo Jaldesa M
International Federation of Gynecology and Obstetrics (FIGO) Working Group for Unsafe Abortion – East, Central and South African Region
Kenya
(African Region)
Abortion care None
Helena Kopp Kallner F
Karolinska Institutet
Sweden
(European Region)
Medical abortion care None
Alongkone Phengsavanh M Faculty of Medicine, University of Health Sciences, Ministry of Health
Lao People’s Democratic Republic
(Western Pacific Region)
Women’s health None
Mariana Romero F
Center for the Study of State and Society
Argentina
(Region of the Americas)
Women’s health None
Stephen Rulisa M
University of Rwanda
Rwanda
(African Region)
Women’s health None
Shahida Zaidi F National Committee for Maternal and Neonatal Health
Pakistan
(Eastern Mediterranean Region)
Abortion care None
* Conflict of interest (COI)
MEMBERS External Review Group (ERG)
For more information, please contact:
Department of Reproductive Health and ResearchWorld Health Organization
Avenue Appia 20, CH-1211 Geneva 27, Switzerland
Fax: +41 22 791 4171
Email: reproductivehealth@who.int
Web: www.who.int/reproductivehealth
ISBN 978-92-4-155040-6
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